Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2.
Long-Term Persistence of Spike Protein Antibody and Predictive Modeling of Antibody Dynamics After Infection With Severe Acute Respiratory Syndrome Coronavirus 2.
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SARS冠状病毒2感染后刺突蛋白抗体的长期持续性和抗体动力学的预测模型。
DOI：
10.1093/cid/ciab607
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发表时间：
2022-04-09
期刊：
影响因子：
--
通讯作者：
COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) team
中科院分区：
文献类型：
--
作者：
Grandjean L;Saso A;Torres Ortiz A;Lam T;Hatcher J;Thistlethwayte R;Harris M;Best T;Johnson M;Wagstaffe H;Ralph E;Mai A;Colijn C;Breuer J;Buckland M;Gilmour K;Goldblatt D;COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) team
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）的抗体已被证明可以在体外中和病毒，并在再次暴露的动物攻击模型中预防疾病。然而，目前对SARS-CoV-2体液动力学和寿命的理解是相互矛盾的。COVID-19工作人员抗体反应测试研究（Co-Stars）前瞻性招募了3679名医护人员，以平行全面表征SARS-CoV-2刺突蛋白（S）、受体结合结构域和核蛋白（N）抗体的动力学。筛选血清学阳性的参与者使用Meso Scale Discovery Assay每月进行一次连续血清学检测，最长持续7个月。生存分析确定了血清逆转的比例，而2个分层伽马模型预测了长期抗体轨迹的上限和下限。从349名血清阳性参与者中共提供了1163份每月样本。在出现症状后200天，>95%的参与者可检测到S抗体，而75%的参与者可检测到N抗体。使用“连续衰减”模型预测在95%的参与者中可检测到S抗体，直到465天（95%置信区间，370-575天），并无限期地使用“衰减到平台”模型来解释长寿浆细胞的抗体分泌。S-抗体滴度与体外替代中和强烈相关（R2 = 0.72）。然而，N抗体迅速衰减，半衰期为60天（95%置信区间，52-68天）。本文提供的Co-Stars数据为中和S抗体的长期持续性提供了证据。这对SARS-CoV-2感染后功能性免疫的持续时间具有重要意义。相反，在未来的血清阳性率研究和公共卫生决策中必须考虑N抗体的快速衰减。这是第一项建立能够预测SARS-CoV-2感染后长期体液动力学的数学框架的研究。NCT 04380896。我们证明了在严重急性呼吸综合征冠状病毒2型感染后长达200天的349名患者的系列样本中刺突蛋白的持续存在和核蛋白抗体的衰减，并提供了一个数学建模框架来预测长期免疫应答。
Antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been shown to neutralize the virus in vitro and prevent disease in animal challenge models on reexposure. However, the current understanding of SARS-CoV-2 humoral dynamics and longevity is conflicting. The COVID-19 Staff Testing of Antibody Responses Study (Co-Stars) prospectively enrolled 3679 healthcare workers to comprehensively characterize the kinetics of SARS-CoV-2 spike protein (S), receptor-binding domain, and nucleoprotein (N) antibodies in parallel. Participants screening seropositive had serial monthly serological testing for a maximum of 7 months with the Meso Scale Discovery Assay. Survival analysis determined the proportion of seroreversion, while 2 hierarchical gamma models predicted the upper and lower bounds of long-term antibody trajectory. A total of 1163 monthly samples were provided from 349 seropositive participants. At 200 days after symptoms, >95% of participants had detectable S antibodies, compared with 75% with detectable N antibodies. S antibody was predicted to remain detectable in 95% of participants until 465 days (95% confidence interval, 370–575 days) using a “continuous-decay” model and indefinitely using a “decay-to-plateau” model to account for antibody secretion by long-lived plasma cells. S-antibody titers were correlated strongly with surrogate neutralization in vitro (R2 = 0.72). N antibodies, however, decayed rapidly with a half-life of 60 days (95% confidence interval, 52–68 days). The Co-Stars data presented here provide evidence for long-term persistence of neutralizing S antibodies. This has important implications for the duration of functional immunity after SARS-CoV-2 infection. In contrast, the rapid decay of N antibodies must be considered in future seroprevalence studies and public health decision-making. This is the first study to establish a mathematical framework capable of predicting long-term humoral dynamics after SARS-CoV-2 infection. NCT04380896. We demonstrate persistence of spike protein and decay of nucleoprotein antibody in serial samples from 349 patients up to 200 days after severe acute respiratory syndrome coronavirus 2 infection and provide a mathematical modeling framework to predict long-term immune responses.
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